scholarly journals Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects

Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 41959-41973 ◽  
Author(s):  
Elisa Neubauer ◽  
Ralph M. Wirtz ◽  
Daniel Kaemmerer ◽  
Maria Athelogou ◽  
Lydia Schmidt ◽  
...  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tatsuki Ishikawa ◽  
Katsunori Nakano ◽  
Masafumi Osaka ◽  
Kenichi Aratani ◽  
Kadotani Yayoi ◽  
...  

Abstract Background  Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. Case presentation We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. Conclusions  GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.


Author(s):  
Pernille Holmager ◽  
Seppo W. Langer ◽  
Birgitte Federspiel ◽  
Gro Linno Willemoe ◽  
Rajendra Singh Garbyal ◽  
...  

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S77-S77
Author(s):  
N C Jadhav ◽  
D L Gang

Abstract Casestudy: Pancreatic neuroendocrine neoplasms (PanNEN) are rare accounting for 2-5% of pancreatic tumors. Although mostly sporadic, 10-20% are associated with inherited syndromes, notably MEN-1, Von Hippel- Lindau disease, neurofibromatosis type 1, and tuberous sclerosis (TS). When compared to sporadic cases, PanNEN in hereditary syndromes occur at a younger age, are often multifocal, cystic, and may show characteristic microscopic patterns. TS is an autosomal dominant multi-system disorder with mutations involving TSC1 or TSC2 genes which function as tumor suppressors by inhibiting mTORC1 kinase. PanNEN is observed in 1.5-1.8% of patients with TS and no surveillance guidelines for the assessment of pancreatic lesions are established. Compared to other syndromes, PanNEN associated with TS are solitary. To our knowledge, only two cases of multifocal PanNEN in TS patients have been reported. We present a case of a 67-year-old gentleman with a history of TS also affecting two daughters. He presented to the emergency department with severe abdominal pain. Abdominal ultrasound suggested acute appendicitis and an incidental 2.0 cm solid lesion was noted in the head of the pancreas. Follow-up MRI revealed two additional non-cystic masses in the pancreatic tail. Endoscopic ultrasound-guided biopsy of a tail lesion revealed monomorphic tumor cells with stippled chromatin without cytologic atypia. Immunohistochemical staining was positive for synaptophysin and chromogranin. Ki-67 labelling index was under 1%. Diagnosis of a well-differentiated neuroendocrine tumor (G1) was made. The patient denied symptoms of the carcinoid syndrome and no biologically active hormones were detected. Gallium PET scan revealed multiple foci of radiotracer uptake throughout the pancreas in addition to those described on MRI. Although PanNEN are rare in TS, malignant behavior has been reported. This case reinforces the importance of early detection through active surveillance, especially as surgical options may be limited in multifocal disease.


2020 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Slmaro Park ◽  
Han-Sung Jung ◽  
Young-Soo Jung ◽  
Woong Nam ◽  
Jung Yul Cha ◽  
...  

Decompression followed by enucleation, which is one of the treatments used for odontogenic keratocysts (OKCs), is frequently used in OKC lesions of large sizes. This method offers the advantage of minimizing the possibility of sensory impairment without creating a wide-range bone defect; moreover, the recurrence rate can be significantly lower than following simple enucleation. This study aimed to assess the changes in histology and expression of proliferation markers in OKCs before and after decompression treatment. A total of 38 OKC tissue samples from 19 patients who had undergone decompression therapy were examined morphologically and immunohistochemically to observe changes in proliferative activity before and after decompression. The markers used for immunohistochemistry (IHC) staining were Bcl-2, epidermal growth factor receptor (EGFR), Ki-67, P53, PCNA, and SMO. The immunohistochemistry positivity of the 6 markers was scored by using software ImageJ, version 1.49, by quantifying the intensity and internal density of IHC-stained epithelium. The values of Bcl-2, Ki-67, P53, proliferating cell nuclear antigen (PCNA), and SMO in OKCs before and after decompression showed no significant change. No correlation between clinical shrinkage and morphologic changes or expression of proliferation and growth markers could be found. There was no statistical evidence that decompression treatment reduces potentially aggressive behavior of OKC within the epithelial cyst lining itself. This might indicate that decompression does not change the biological behavior of the epithelial cyst lining or the recurrence rate.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 277
Author(s):  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Henning Jann ◽  
Anja Rinke ◽  
Sebastian Krug

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases.


2021 ◽  
Vol 32 (1) ◽  
pp. 154-168 ◽  
Author(s):  
Marco Volante ◽  
Ozgur Mete ◽  
Giuseppe Pelosi ◽  
Anja C. Roden ◽  
Ernst Jan M. Speel ◽  
...  

AbstractThoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.


2016 ◽  
Vol 57 (12) ◽  
pp. 1851-1857 ◽  
Author(s):  
C. B. Johnbeck ◽  
U. Knigge ◽  
S. W. Langer ◽  
A. Loft ◽  
A. K. Berthelsen ◽  
...  

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